Arenaviruses (AV) are rodent-borne viruses that cause an acute and often fatal hemorrhagic fever with associated malaise, severe edema, blood loss and a high mortality rate. Lassa virus (LASV) is an Old World arenavirus endemic to regions of West Africa. Imported cases of Lassa fever have been reported in the United States, Europe and Canada. It is estimated that between 300,000 and 500,000 cases of Lassa fever occur each year, with mortality rates of 15%-20% in hospitalized patients. New World arenaviruses, Junin (JUNV), Machupo (MACV), Guanarito, and Sabia viruses, are endemic to South America and are known to cause thousands of cases of severe hemorrhagic fever per year. Arena viruses are CDC Category A biological threat agents, and in the unfortunate event of an emerging disease outbreak or bioterror attack with these viruses there would be no FDA approved pre- or post-exposure therapeutic or vaccine available to the public. There has been reported studies that have identified HLA class I-restricted epitopes that can elicit an immune response in mice. See Botten, J., et al., J. Vir. 9947-9956 (October 2010).
For all the recent attention given to arenaviruses due to the outbreaks and the high degree of morbidity and mortality, there are very few treatments available. No licensed vaccine exists for AV prophylaxis and the only licensed drug for treatment of human AV infection is the anti-viral drug ribavirin. Ribavirin helps reduce morbidity and mortality associated with AV infection if taken early on exposure, but suffers from high toxicity and side effects. There is a clear unmet need to develop low cost and/or efficacious drugs for treatment and effective vaccines for prophylaxis in the AV endemic areas of the world as well as for combating exposure via a biodefense threat or through deployment of US military personnel in endemic parts of the world.
Furthermore, there also exists an unmet need for a multiagent arenavirus vaccine. As noted earlier there are no competitive effective prophylaxes or therapies available. To our knowledge the Junin live attenuated virus vaccine (Candid #1) approved for limited use under an investigational new drug (IND) status by the FDA is the only vaccine tested for arena virus infections. However, this vaccine was also subsequently shown in animal studies to not be able to cross-protect against other arenavirus strains.
Thus, there remains a need for a vaccine that provides an efficacious drug or effective vaccine for arenaviruses, and a vaccine that targets multiple arenavirus agents singly or simultaneously.